[MS11] Dynamics of Pattern Formation and Morphogenesis in Biological Systems

[MS11-06] Mechanics-induced Cell-Cycle Synchronization and the Emergence of Tissue Homeostasis

*Yuting Lou¹, Tetsuya Hiraiwa³, Yusuke Toyama² (1. Fudan University (China), 2. National University of Singapore (Singapore), 3. Academia Sinica (Taiwan))

Keywords:

tissue homeostasis,cell cycle,oscillator

Epithelial tissues are composed of cells in tight contact and essentially regulated by confluent tissue mechanics. In the near decades, accumulating evidence has shown that mechanical forces existing in epithelia contribute to the regulation of cell death and division through mechanotransduction. Mechanical properties such as viscoelasticity of cellular matters and deformability of cytoskeleton dictate the force transmissions across the tissues and give rise to phase transitions between fluid and solid states of tissues. Despite that research on the interplay of mechanics and cellular behaviors has been mainly applied to early-stage morphogenesis, how tissue homeostasis could emerge from such interplay remains unexplored. To address this fundamental question, we propose a prototypic framework, where a minimal tissue confluent mechanics model is constructed via self-propelled Voronoi cells with the mechanical energy defined with nearest neighbor interactions, and the cells are further equipped with a cell cycle regulator in the type of Kuramoto oscillator. By assuming some principles in the interplay between cell mechanical energy and cell cycle progression, we could simulate tissue homeostasis in different spatial-temporal patterns of cell-cycle synchronization. We compared them to the FUCCI marker of cell cycles collected in in vitro epithelial monolayers and found that while global synchronization is always favored in the simulation, the in vitro samples show robust localized synchronization. By exploring the interplay between the mechanics and cycle regulators in silico, we studied the possible mechanisms behind robust localized synchronizations and gained insights into the role of mechanics in the maintenance of tissue homeostasis